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Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT).

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タイトル: Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT).
著者: Kyo, Satoru 著作を一覧する
Takakura, Masahiro 著作を一覧する
Taira, Takahiro 著作を一覧する
Kanaya, Taro 著作を一覧する
Itoh, Hideaki 著作を一覧する
Yutsudo, Masuo 著作を一覧する
Ariga, Hiroyoshi 著作を一覧する
Inoue, Masaki 著作を一覧する
発行日: 2000年 2月 1日
出版者: Oxford University Press
誌名: Nucleic acids research
巻: 28
号: 3
開始ページ: 669
終了ページ: 677
出版社 DOI: 10.1093/nar/28.3.669
抄録: Telomerase activation is thought to be a critical step in cellular immortalization and carcinogenesis. The human telomerase catalytic subunit (hTERT) is a rate limiting determinant of the enzymatic activity of human telomerase. In the previous study, we identified the proximal 181 bp core promoter responsible for transcriptional activity of the hTERT gene. To identify the regulatory factors of transcription, transient expression assays were performed using hTERT promoter reporter plasmids. Serial deletion assays of the core promoter revealed that the 5'-region containing the E-box, which binds Myc/Max, as well as the 3'-region containing the GC-box, which binds Sp1, are essential for transactivation. The mutations introduced in the E-box or GC-box significantly decreased transcriptional activity of the promoter. Overexpression of Myc/Max or Sp1 led to significant activation of transcription in a cell type-specific manner, while Mad/Max introduction repressed it. However, the effects of Myc/Max on transactivation were marginal when Sp1 sites were mutated. Western blot analysis using various cell lines revealed a positive correlation between c-Myc and Sp1 expression and transcriptional activity of hTERT. Using fibroblast lineages in different stages of transformation, we found that c-Myc and Sp1 were induced to a dramatic extent when cells overcame replicative senescence and obtained immortal characteristics, in association with telomerase activation. These findings suggest that c-Myc and Sp1 cooperatively function as the major determinants of hTERT expression, and that the switching functions of Myc/Max and Mad/Max might also play roles in telomerase regulation.
Relation (URI):
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 有賀 寛芳


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